Devices, systems, and methods for treatment of intracranial aneurysms

ABSTRACT

Systems and methods for treating an aneurysm in accordance with embodiments of the present technology include intravascularly delivering an occlusive member to an aneurysm cavity and deforming a shape of the occlusive member via introduction of an embolic element to a space between the occlusive member and an inner surface of the aneurysm wall.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application claims the benefit of priority of U.S.Provisional Application No. 62/930,421, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,487, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,303, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,324, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,333, filed Nov. 4, 2019, and U.S.Provisional Application No. 62/930,357, filed Nov. 4, 2019, each ofwhich is incorporated by reference herein in its entirety.

The following applications are also incorporated by reference herein intheir entireties: U.S. patent application Ser. No. 16/949,568, filedconcurrently herewith, and titled DEVICES, SYSTEMS, AND METHODS FORTREATMENT OF INTRACRANAIL ANEURYSMS; U.S. patent application Ser. No.16/949,561, filed concurrently herewith, and titled SYSTEMS AND METHODSFOR TREATING ANEURYSMS; U.S. patent application Ser. No. 16/949,561,filed concurrently herewith, and titled SYSTEMS AND METHODS FOR TREATINGANEURYSMS U.S. patent application Ser. No. 16/949,564, filedconcurrently herewith, and titled SYSTEMS AND METHODS FOR TREATINGANEURYSMS; U.S. patent application Ser. No. 16/949,565, filedconcurrently herewith, and titled ANEURYSM TREATMENT DEVICE; U.S. patentapplication Ser. No. 16/949,569, filed concurrently herewith, and titledDEVICES, SYSTEMS, AND METHODS FOR TREATING OF INTRACRANIAL ANEURYSMS;U.S. patent application Ser. No. 16/949,566, filed concurrentlyherewith, and titled SYSTEMS AND METHODS FOR TREATING ANEURYSMS; U.S.patent application Ser. No. 16/949,570, filed concurrently herewith, andtitled DEVICES, SYSTEMS, AND METHODS FOR TREATING ANEURYSMS;International Application No. PCT/US2020/070743, filed concurrentlyherewith, titled DEVICES, SYSTEMS, AND METHODS FOR TREATMENT OFINTRACRANIAL ANEURYSMS; International Application No. PCT/US2020/070741,filed concurrently herewith, titled DEVICES, SYSTEMS, AND METHODS FORTREATMENT OF INTRACRANIAL ANEURYSMS; and International Application No.PCT/US2020/070742, filed concurrently herewith, titled SYSTEMS ANDMETHODS FOR TREATING ANEURYSMS.

TECHNICAL FIELD

The present technology relates to systems, devices, and methods fortreating intracranial aneurysms.

BACKGROUND

An intracranial aneurysm is a portion of an intracranial blood vesselthat bulges outward from the blood vessel's main channel. This conditionoften occurs at a portion of a blood vessel that is abnormally weakbecause of a congenital anomaly, trauma, high blood pressure, or foranother reason. Once an intracranial aneurysm forms, there is asignificant risk that the aneurysm will eventually rupture and cause amedical emergency with a high risk of mortality due to hemorrhaging.When an unruptured intracranial aneurysm is detected or when a patientsurvives an initial rupture of an intracranial aneurysm, vascularsurgery is often indicated. One conventional type of vascular surgeryfor treating an intracranial aneurysm includes using a microcatheter todispose a platinum coil within an interior volume of the aneurysm. Overtime, the presence of the coil should induce formation of a thrombus.Ideally, the aneurysm's neck closes at the site of the thrombus and isreplaced with new endothelial tissue. Blood then bypasses the aneurysm,thereby reducing the risk of aneurysm rupture (or re-rupture) andassociated hemorrhaging. Unfortunately, long-term recanalization (i.e.,restoration of blood flow to the interior volume of the aneurysm) afterthis type of vascular surgery occurs in a number of cases, especiallyfor intracranial aneurysms with relatively wide necks and/or relativelylarge interior volumes.

Another conventional type of vascular surgery for treating anintracranial aneurysm includes deploying a flow diverter within theassociated intracranial blood vessel. The flow diverter is often a meshtube that causes blood to preferentially flow along a main channel ofthe blood vessel while blood within the aneurysm stagnates. The stagnantblood within the aneurysm should eventually form a thrombus that leadsto closure of the aneurysm's neck and to growth of new endothelialtissue, as with the platinum coil treatment. One significant drawback offlow diverters is that it may take weeks or months to form aneurysmalthrombus and significantly longer for the aneurysm neck to be coveredwith endothelial cells for full effect. This delay may be unacceptablewhen risk of aneurysm rupture (or re-rupture) is high. Moreover, flowdiverters typically require antiplatelet therapy to prevent a thrombusfrom forming within the main channel of the blood vessel at the site ofthe flow diverter. Antiplatelet therapy may be contraindicated shortlyafter an initial aneurysm rupture has occurred because risk ofre-rupture at this time is high and antiplatelet therapy tends toexacerbate intracranial hemorrhaging if re-rupture occurs. For these andother reasons, there is a need for innovation in the treatment ofintracranial aneurysms. Given the severity of this condition, innovationin this field has immediate life-saving potential.

SUMMARY

The subject technology is illustrated, for example, according to variousaspects described below, including with reference to FIGS. 1A-5B.Various examples of aspects of the subject technology are described asnumbered clauses (1, 2, 3, etc.) for convenience. These are provided asexamples and do not limit the subject technology.

1. A method for treating an aneurysm, the method comprising:

-   -   positioning a distal end of an elongated shaft in an aneurysm        cavity;    -   releasing an occlusive member from the elongated shaft while the        distal end of the elongated shaft is positioned within the        aneurysm cavity such that the occlusive member self-expands to        assume a first expanded state in which the occlusive member        forms a first shape, wherein, in the first expanded state, the        occlusive member encloses an interior region having a first        interior volume; and    -   delivering an embolic element between the occlusive member and        the aneurysm wall to transform the occlusive member into a        second expanded state in which the occlusive member defines a        second interior volume less than the first interior volume,        wherein the occlusive member forms a second shape in the second        expanded state that is different than the first shape in the        first expanded state.

2. The method of any one of the previous Clauses, wherein transformingthe occlusive member into the second expanded shape includes injectingthe embolic material to urge a portion of a sidewall of the expandablemesh in a direction away from a wall of the aneurysm and towards theinterior region of the occlusive member.

3. The method of any one of the previous Clauses, wherein transformingthe occlusive member into the second expanded shape includes injectingthe embolic material to invert a portion of a sidewall of the occlusivemember such that the portion is convex towards the aneurysm wall in thefirst expanded state and concave towards the aneurysm wall in the secondexpanded state.

4. The method of any one of the previous Clauses, wherein the embolicelement comprises a liquid embolic.

5. The method of any one of the previous Clauses, wherein the embolicelement comprises one or more embolization coils.

6. The method of any one of the previous Clauses, wherein delivering theembolic element occurs after the occlusive member is in the firstexpanded state.

7. The method of any one of the preceding Clauses, wherein the occlusivemember is a mesh.

8. The method of any one of the preceding Clauses, wherein the occlusivemember is a braid.

9. The method of any one of the preceding Clauses, wherein the occlusivemember is a dual-layered braid.

10. The method of any one of the preceding Clauses, wherein theocclusive member has a globular or generally spherical shape in thefirst expanded state.

11. The method of any one of the preceding Clauses, wherein theocclusive member is cup or bowl-shaped in the second expanded state.

12. The method of any one of the preceding Clauses, wherein the secondshape is a predetermined three-dimensional shape.

13. The method of any one of the preceding Clauses, wherein theocclusive member forms a multi-layer braid at the neck of the aneurysmin the second expanded state.

14. The method of any one of the previous Clauses, wherein the occlusivemember comprises a plurality of braided filaments that assume a pre-set,three-dimensional shape in the expanded state.

15. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of 24, 32, 36, 48, 64, or 72 filaments.

16. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, some or all ofwhich have a diameter of about 0.001 inches (0.00254 cm).

17. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, some or all ofwhich have the same diameter.

18. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, at least someof which have different diameters.

19. The method of any one of the previous Clauses, wherein the occlusivemember forms a closed, globular shape in the expanded state, the meshhaving an aperture at a distal portion.

20. The method of any one of the previous Clauses, wherein, in theexpanded state, the occlusive member forms one of a sphere, a prolatespheroid, or an oblate spheroid.

21. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer.

22. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer that meet at a foldat a distal portion of the occlusive member.

23. The method of Clause 22, wherein the expandable mesh includes anaperture at a distal portion, the aperture being defined by the fold.

24. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer that meet at a foldat a proximal portion of the occlusive member.

25. The method of Clause 24, wherein the expandable mesh includes anaperture at a distal portion, the aperture being defined by the fold.

26. The method of any one of the previous Clauses, wherein the occlusivemember has a maximum cross-sectional dimension of 3.0 mm, 3.5 mm, 4.0mm, 4.5 mm, 5.0 mm, 5.5 mm, 6.0 mm, 6.5 mm, 7.0 mm, 7.5 mm, or 8.0 mm.

27. The method of any one of the previous Clauses, wherein the occlusivemember is formed of a plurality of filaments having first and secondends fixed at a coupler.

28. The method of any one of the previous Clauses, wherein the occlusivemember is formed of a plurality of filaments formed of an inner corematerial surrounded by an outer material.

29. The method of Clause 28, wherein the inner core material is aradiopaque material and the outer material is a superelastic material.

30. The method of any one of the previous Clauses, wherein the occlusivemember is a laser-cut tube.

31. The method of any one of the previous Clauses, wherein the occlusivemember comprises a plurality of filaments.

32. The method of Clause 31, wherein the filaments are interwoven.

33. The method of Clause 31 or Clause 32, wherein the filaments arebraided.

34. The method of any one of Clauses 31 to 33, wherein each of thefilaments has a first end and a second end opposite the first end, andwherein both the first and second ends of the filaments are fixedrelative to one another at a coupler.

35. The method of Clause 34, wherein the coupler is disposed at a distalend of the occlusive member.

36. The method of Clause 34, wherein the coupler is disposed at aproximal end of the occlusive member.

37. The method of any one of Clauses 31 to 36, wherein each of thefilaments terminate at only one end of the occlusive member.

38. The method of Clause 37, wherein the filaments form an opening at anend of the occlusive member opposite the only one end.

39. The method of Clause 38, wherein an inverted portion of each of thefilaments define the opening.

40. The method of Clause 39, wherein the inverted portions of thefilaments are configured to move relative to one another.

41. The method of any one of the previous Clauses, wherein the embolicelement comprises a biopolymer and a chemical crosslinking agent.

42. The method of Clause 42, wherein the biopolymer includes chitosan, aderivative of chitosan, an analog of chitosan, or a combination thereof.

43. The method of Clause 42 or Clause 43, wherein the chemicalcrosslinking agent includes genipin, a derivative of genipin, an analogof genipin, or a combination thereof.

44. The method of any one of Clauses 42 to 44, wherein the embolicelement further comprises a physical crosslinking agent.

45. The method of Clause 45, the physical crosslinking agent includes βglycerophosphate, a derivative of β glycerophosphate, an analog of βglycerophosphate, or a combination thereof.

46. The method of Clause 42, wherein the biopolymer includes chitosan, aderivative of chitosan, an analog of chitosan, or a combination thereof;

-   -   the chemical crosslinking agent includes genipin, a derivative        of genipin, an analog of genipin, or a combination thereof; and        the physical crosslinking agent includes β glycerophosphate, a        derivative of β glycerophosphate, an analog of β        glycerophosphate, or a combination thereof.

47. The method of any one of the preceding Clauses, wherein the embolicelement comprises a contrast agent.

48. The method of Clause 48, wherein the contrast agent is selected toprovide diminishing radiopacity.

49. The method of Clause 48 or Clause 49, wherein the contrast agentincludes iohexol, a derivative of iohexol, an analog of iohexol, or acombination thereof.

50. A method for treating an aneurysm, the method comprising:

-   -   positioning an expandable occlusive member in an initial        expanded state within an aneurysm, wherein in the initial        expanded state the expandable occlusive member provides a number        of layers across a neck of the aneurysm; and    -   doubling the number of layers of the occlusive device across the        neck of the aneurysm by introducing an embolic element to the        aneurysm cavity.

51. The method of Clause 51, wherein the number of layers is one.

52. The method of Clause 51, wherein the number of layers is two.

53. The method of any one of Clauses 51 to 53, wherein the layers aremesh layers.

54. The method of any one of Clauses 51 to 54, wherein the occlusivemember has a first shape in the initial expanded state, and whereinintroducing the embolic element transforms the occlusive member from theinitial expanded state to a secondary expanded state in which theocclusive member forms a second shape different than the first shape.

55. The method of Clause 55, wherein a volume enclosed by the firstshape is greater than a volume enclosed by the second shape.

56. A method for imaging treatment of an aneurysm, the methodcomprising:

-   -   acquiring a first image visualizing:        -   an occlusive member positioned within an aneurysm, the            occlusive member including a first radiopaque marker; and        -   a conduit having a distal portion positioned within an            aneurysm, the distal portion of the conduit including a            second radiopaque marker; and    -   acquiring a second image in which the first radiopaque marker is        further from the second radiopaque marker than in the first        image.

57. The method of Clause 56, wherein, in the second image, the firstradiopaque marker is positioned proximal to the second radiopaquemarker.

58. The method of one of Clauses 56 to 57, wherein, in the second image,the first radiopaque marker is positioned closer to a neck of theaneurysm than in the first image.

59. The method of any one of Clauses 56 to 58, wherein, in the firstimage, the first radiopaque marker is positioned in a distal half of theocclusive member.

60. The method of any one of Clauses 56 to 59, wherein, in the firstimage, the first radiopaque marker is positioned on a distal-facingsurface of the occlusive member.

61. The method of any one of Clauses 56 to 60, wherein, in the firstimage, the first radiopaque marker is positioned proximal to the secondradiopaque marker.

62. The method of any one of Clauses 56 to 61, wherein, in the firstimage and in the second image, the second radiopaque marker is disposednearer to a dome of the aneurysm than the first radiopaque marker.

63. The method of any one of Clauses 56 to 62, wherein, in the secondimage, a radiopaque occlusive element is visible in a space between thefirst radiopaque marker and the second radiopaque marker.

64. The method of any one of Clauses 56 to 63, further comprisingacquiring a third image in which the first radiopaque marker is furtherfrom the second radiopaque marker than in the second image.

65. The method of any one of Clauses 56 to 64, wherein acquiring thefirst image and acquiring the second image each comprises acquiring afluoroscopic image.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present disclosure can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present disclosure.

FIG. 1A shows a perspective view of a system for treating an aneurysm inaccordance with the present technology.

FIG. 1B shows an enlarged view of a distal portion of the treatmentsystem of FIG. 1A in accordance with the present technology.

FIGS. 1C and 1D are sectioned views of occlusive members in an expandedstate in accordance with the present technology.

FIG. 2 shows an embolic kit according to the present technology.

FIGS. 3A-3G depict an example method of treating an aneurysm with thetreatment systems of the present technology.

FIGS. 4A-5B show various types of images that may be employed to confirmand/or monitor deployment of the treatment system of the presenttechnology.

DETAILED DESCRIPTION

Methods for treating intracranial aneurysms in accordance with at leastsome embodiments of the present technology include positioning anexpandable occlusive member within the aneurysm and introducing anembolic element between the occlusive member and an aneurysm wall.Introduction of the embolic element both fills space within the aneurysmcavity and deforms the occlusive member from a first expanded state to asecond expanded state to fortify the occlusive member at the neck of theaneurysm. Deformation of the occlusive member from a first expandedstate to a second expanded state provides the additional advantage ofgiving visual confirmation to the physician that the delivered amount ofembolic element sufficiently fills the aneurysm cavity. In addition toproviding a structural support and anchor for the embolic element, theocclusive member provides a scaffold for tissue remodeling and divertsblood flow from the aneurysm. Moreover, the embolic element exerts asubstantially uniform pressure on the occlusive member towards the neckof the aneurysm, thereby pressing the portions of the occlusive memberpositioned adjacent the neck against the inner surface of the aneurysmwall such that the occlusive member forms a complete and stable seal atthe neck.

Specific details of systems, devices, and methods for treatingintracranial aneurysms in accordance with embodiments of the presenttechnology are described herein with reference to FIGS. 1A-5B. Althoughthese systems, devices, and methods may be described herein primarily orentirely in the context of treating saccular intracranial aneurysms,other contexts are within the scope of the present technology. Forexample, suitable features of described systems, devices, and methodsfor treating saccular intracranial aneurysms can be implemented in thecontext of treating non-saccular intracranial aneurysms, abdominalaortic aneurysms, thoracic aortic aneurysms, renal artery aneurysms,arteriovenous malformations, tumors (e.g. via occlusion of vessel(s)feeding a tumor), perivascular leaks, varicose veins (e.g. via occlusionof one or more truncal veins such as the great saphenous vein),hemorrhoids, and sealing endoleaks adjacent to artificial heart valves,covered stents, and abdominal aortic aneurysm devices among otherexamples. Furthermore, it should be understood, in general, that othersystems, devices, and methods in addition to those disclosed herein arewithin the scope of the present disclosure. For example, systems,devices, and methods in accordance with embodiments of the presenttechnology can have different and/or additional configurations,components, procedures, etc. than those disclosed herein. Moreover,systems, devices, and methods in accordance with embodiments of thepresent disclosure can be without one or more of the configurations,components, procedures, etc. disclosed herein without deviating from thepresent technology.

I. Overview of Systems of the Present Technology

FIG. 1A illustrates a view of a system 10 for treating intracranialaneurysms according to one or more embodiments of the presenttechnology. As shown in FIG. 1A, the system 10 comprises a treatmentsystem 100 and an embolic kit 200 for use with one or more components ofthe treatment system 100. The treatment system 100 may comprise anocclusive member 102 (shown in an expanded state) detachably coupled toa delivery system, and the delivery system may be configured tointravascularly position the occlusive member 102 within an aneurysm.The embolic kit 200 may comprise one or more substances or devices thatalone or in combination form an embolic element that is configured toco-occupy the internal volume of the aneurysm with the occlusive member102. In some embodiments, the treatment system 100 may be configured todeliver the embolic element (and/or one or more precursors thereof) tothe aneurysm. Additionally or alternatively, the system 10 may include aseparate delivery system (not shown) for delivering the embolic element(and/or one or more precursors thereof) to the aneurysm cavity.

As shown in FIG. 1A, the treatment system 100 has a proximal portion 100a configured to be extracorporeally positioned during treatment and adistal portion 100 b configured to be intravascularly positioned withina blood vessel (such as an intracranial blood vessel) at a treatmentsite at or proximate an aneurysm. The treatment system 100 may include ahandle 103 at the proximal portion 100 a, the occlusive member 102 atthe distal portion 100 b, and a plurality of elongated shafts or membersextending between the proximal and distal portions 100 a and 100 b. Insome embodiments, such as that shown in FIG. 1A, the treatment system100 may include a first elongated shaft 109 (such as a guide catheter orballoon guide catheter), a second elongated shaft 108 (such as amicrocatheter) configured to be slidably disposed within a lumen of thefirst elongated shaft 109, and an elongated member 106 configured to beslidably disposed within a lumen of the second elongated shaft 108. Insome embodiments, the treatment system 100 does not include the firstelongated shaft 109 and only includes the second elongated shaft 108.

FIG. 1B is an enlarged view of the distal portion 100 b of the treatmentsystem 100. Referring to FIGS. 1A and 1B together, the occlusive member102 may be detachably coupled to a distal end of the elongated member106. For example, the elongated member 106 may include a first coupler112 at its distal end, and the occlusive member 102 may include a secondcoupler 114 configured to detachably couple with the first coupler 112.The treatment system 100 may further comprise a conduit 116 extendingfrom the handle 103 (for example, via port 110) distally to the distalportion 100 b of the treatment system 100. The conduit 116 is configuredto deliver the embolic element (and/or one or more precursors thereof)through one or more components of the delivery system (e.g., the firstor second elongated shafts 109, 108, the elongated member 106, etc.) toa position at the exterior of the occlusive member 102. As such, theembolic element may be positioned between the occlusive member 102 andan inner wall of the aneurysm cavity, as described in greater detailbelow.

According to some embodiments, the second elongated shaft 108 isgenerally constructed to track over a conventional guidewire in thecervical anatomy and into the cerebral vessels associated with the brainand may also be chosen according to several standard designs that aregenerally available. Accordingly, the second elongated shaft 108 canhave a length that is at least 125 cm long, and more particularly may bebetween about 125 cm and about 175 cm long. In some embodiments, thesecond elongated shaft 108 may have an inner diameter of about 0.015inches (0.0381 cm), 0.017 inches (0.043 cm), about 0.021 inches (0.053cm), or about 0.027 inches (0.069 cm). Other designs and dimensions arecontemplated.

The elongated member 106 can be movable within the first and/or secondelongated shafts 109, 108 to position the occlusive member 102 at adesired location. The elongated member 106 can be sufficiently flexibleto allow manipulation, e.g., advancement and/or retraction, of theocclusive member 102 through tortuous passages. Tortuous passages caninclude, for example, catheter lumens, microcatheter lumens, bloodvessels, urinary tracts, biliary tracts, and airways. The elongatedmember 106 can be formed of any material and in any dimensions suitablefor the task(s) for which the system is to be employed. In someembodiments, the elongated member 106 can comprise a solid metal wire.In some embodiments, the elongated member 106 may comprise any othersuitable form of shaft such as an elongated tubular shaft.

In some embodiments, the elongated member 106 can comprise stainlesssteel, nitinol, or other metal or alloy. In some embodiments, theelongated member 106 can be surrounded over some or all of its length bya coating, such as, for example, polytetrafluoroethylene. The elongatedmember 106 may have a diameter that is generally constant along itslength, or the elongated member 106 may have a diameter that tapersradially inwardly, along at least a portion of its length, as it extendsin a distal direction.

According to several embodiments, the conduit 116 may be a catheter orelongated shaft that is delivered separately from the second elongatedshaft 108.

A. Selected Examples of Occlusive Members

FIG. 1C is a sectioned view of the occlusive member 102, shown in anexpanded state and detached from the treatment system 100. Referring toFIGS. 1B and 1C, the occlusive member 102 may comprise an expandableelement having a low-profile or constrained state while positionedwithin a catheter (such as the second elongated shaft 108) for deliveryto the aneurysm and an expanded state in which the expandable element isconfigured to be positioned within an aneurysm (such as a cerebralaneurysm).

According to some embodiments, the occlusive member 102 may comprise amesh 101 formed of a plurality of braided filaments that have beenheat-set to assume a predetermined shape enclosing an interior volume130 when the mesh 101 is in an expanded, unconstrained state. Exampleshapes include a globular shape, such as a sphere, a prolate spheroid,an oblate spheroid, and others. As depicted in FIG. 1C, the mesh 101 mayhave inner and outer layers 122, 124 that have proximal ends fixedrelative to one another at the second coupler 114 and meet distally at adistal fold 128 surrounding an aperture 126. While the inner and outerlayers 122, 124 are depicted spaced apart from one another along theirlengths, the inner and outer layers 122, 124 may be in contact with oneanother along all or a portion of their lengths. For example, the innerlayer 122 may press radially outwardly against the outer layer 124. Insome embodiments, the occlusive member 102 may be formed of a singlelayer or mesh or braid.

In some embodiments, the inner and outer layers 122, 124 have theirdistal ends fixed relative to one another at a distal coupler and meetproximally at a proximal fold surrounding an aperture. In any case, insome embodiments the conduit 116 may be configured to be slidablypositioned through some or all of the second coupler 114, the interiorvolume 130 of the expanded mesh 101, and the opening 126.

The inner and outer layers 122 and 124 may conform to one another at thedistal portion (for example as shown in FIG. 1C) to form a curved distalsurface. For example, at least at the distal portion of the occlusivemember 102, the inner and outer layers 122 and 124 may extend distallyand radially inwardly, towards the aperture 126. In some embodiments,the outer and/or inner layers 122 and 124 extend distally and radiallyoutwardly from the second coupler 114, then extend distally and radiallyinwardly up to a distal terminus of the occlusive member 102 (e.g., thefold 128). The occlusive member 102 and/or layers thereof may be curvedalong its entire length, or may have one or more generally straightportions. In some embodiments, the curved surface transitions to a flator substantially flat, distal-most surface that surrounds the aperture126. In some embodiments, the curved surface transitions to adistal-most surface that surrounds the aperture 126 and has a radius ofcurvature that is greater than the average radius of curvature of therest of the occlusive member 102. Having a flat or substantially flatdistal surface, or a distal surface with a radius of curvature that isgreater than the average radius of curvature of the rest of theocclusive member 102, may be beneficial for delivering the embolicelement 230 in that it creates a small gap between the distal surface ofthe occlusive member 102 and the dome of the aneurysm A (see, forexample, FIG. 3B). In some embodiments, the surface of the occlusivemember 102 surrounding the aperture 126 is curved and/or has generallythe same radius of curvature as the remainder of the occlusive member102.

In any case, the inner layer 124 may have a shape that substantiallyconforms to the shape of the outer layer 124, or the inner and outerlayers 122, 124 may have different shapes. For example, as shown in FIG.1D, the inner layer 122 may have a diameter or cross-sectional dimensionthat is less than the outer layer 124. Such a configuration may bebeneficial in that the embolic element 230 experiences less resistance,at least initially, when pushing the distal wall of the occlusion member102 downwardly towards the neck (as described in greater detail below).

In any case, both the proximal portion and the distal portion of themesh 101 can form generally closed surfaces. However, unlike at theproximal portion of the mesh 101, the portion of the filaments at ornear the fold 128 at the distal portion of the mesh 101 can moverelative to one another. As such, the distal portion of the mesh 101 hasboth the properties of a closed end and also some properties of an openend (like a traditional stent), such as some freedom of movement of thedistal-most portions of the filaments and an opening through which theconduit 116, a guidewire, guidetube, or other elongated member may passthrough.

In some embodiments, each of the plurality of filaments have a first endpositioned at the proximal portion of the mesh 101 and a second end alsopositioned at the proximal portion of the mesh 101. Each of thefilaments may extend from its corresponding first end distally along thebody of the mesh 101 to the fold 128, invert, then extend proximallyalong the mesh body to its corresponding second end at the proximalportion of the mesh 101. As such, each of the plurality of filamentshave a first length that forms the inner layer 122 of the mesh 101, asecond length that forms the outer layer 124 of the mesh 101, and bothfirst and second ends fixed at the proximal portion of the mesh 101. Insome embodiments, the occlusive member 102 may comprise a mesh formed ofa single layer, or a mesh formed of three or more layers.

In some embodiments, the distal end surface of the mesh 101 iscompletely closed (i.e., does not include an aperture). In someembodiments the filaments are fixed relative to the at both the proximaland distal ends of the occlusive member 102.

The mesh 101 may be formed of metal wires, polymer wires, or both, andthe wires may have shape memory and/or superelastic properties. The mesh101 may be formed of 24, 32, 36, 48, 64, 72, 96, 128, or 144 filaments.The mesh 101 may be formed of a range of filament or wire sizes, such aswires having a diameter of from about 0.0004 inches to about 0.0020inches, or of from about 0.0009 inches to about 0.0012 inches. In someembodiments, each of the wires or filaments have a diameter of about0.0004 inches, about 0.0005 inches, about 0.0006 inches, about 0.0007inches, about 0.0008 inches, about 0.0009 inches, about 0.001 inches,about 0.0011 inches, about 0.0012 inches, about 0.0013 inches, about0.0014 inches, about 0.0015 inches, about 0.0016 inches, about 0.0017inches, about 0.0018 inches, about 0.0019 inches, or about 0.0020inches. In some embodiments, all of the filaments of the braided mesh101 may have the same diameter. For example, in some embodiments, all ofthe filaments have a diameter of about 0.001 inches. In someembodiments, some of the filaments may have different cross-sectionaldiameters. For example, some of the filaments may have a slightlythicker diameter to impart additional strength to the braided layers. Insome embodiments, some of the filaments can have a diameter of about0.001 inches, and some of the filaments can have a diameter of greaterthan 0.001 inches. The thicker filaments may impart greater strength tothe braid without significantly increasing the device delivery profile,with the thinner wires offering some strength while filling-out thebraid matrix density.

The occlusive member 102 can have different shapes and sizes in anexpanded, unconstrained state. For example, the occlusive member 102 mayhave a bullet shape, a barrel-shape, an egg shape, a dreidel shape, abowl shape, a disc shape, a cylindrical or substantially cylindricalshape, a barrel shape, a chalice shape, etc.

B. Selected Examples of Embolic Kits

The embolic kit 200 may include one or more precursors for creation of aliquid embolic. For example, the embolic kit 200 may include a firstcontainer 202 containing a first precursor material 203 (shownschematically), a second container 204 containing a second precursormaterial 205 (also shown schematically), and a mixing device 206suitable for mixing the first and second precursor materials 203, 205.The mixing device 206 can include mixing syringes 208 (individuallyidentified as mixing syringes 208 a, 208 b) and a coupler 210 extendingbetween respective exit ports (not shown) of the mixing syringes 208.The mixing syringes 208 a, 208 b each include a plunger 212 and a barrel214 in which the plunger 212 is slidably received.

The embolic kit 200 can further include an injection syringe 216configured to receive a mixture of the first and second precursormaterials 203, 205 and deliver the mixture to a proximal portion 100 bof the treatment assembly 100. The injection syringe 216 can include abarrel 220, an exit port 222 at one end of the barrel 220, and a plunger224 slidably received within the barrel 220 via an opposite end of thebarrel 220. The handle 103 of the treatment system 100 may have acoupler configured to form a secure fluidic connection between the lumenand the exit port 222 of the injection syringe 216.

The first and second precursor materials 203, 205 can include abiopolymer and a chemical crosslinking agent, respectively. The chemicalcrosslinking agent can be selected to form covalent crosslinks betweenchains of the biopolymer. In some embodiments, the biopolymer of thefirst precursor material 203 includes chitosan or a derivative or analogthereof, and the chemical crosslinking agent of the second precursormaterial 205 includes genipin or a derivative or analog thereof. Othersuitable crosslinking agents for use with chitosan includeglutaraldehyde, functionalized polyethylene glycol, and derivatives andanalogs thereof. In other embodiments, the biopolymer of the firstprecursor material 203 can include collagen or a derivative or analogthereof, and the chemical crosslinking agent of the second precursormaterial 205 can include hexamethylene diisocyanate or a derivative oranalog thereof. Alternatively or in addition, genipin or a derivative oranalog thereof can be used as a chemical crosslinking agent for acollagen-based biopolymer. In still other embodiments, the biopolymer ofthe first precursor material 203 and the chemical crosslinking agent ofthe second precursor material 205 can include other suitable compoundsalone or in combination.

Mixing the biopolymer of the first precursor material 203 and thechemical crosslinking agent of the second precursor material 205 caninitiate chemical crosslinking of the biopolymer. After the first andsecond precursor materials 203, 205 are mixed, chemical crosslinking ofthe biopolymer occurs for enough time to allow the resulting embolicelement 230 be delivered to the aneurysm before becoming too viscous tomove through the lumen of the conduit 116. In addition, the period oftime during which chemical crosslinking of the biopolymer occurs can beshort enough to reach a target deployed viscosity within a reasonabletime (e.g., in the range of 10-60 minutes; or at most 40 minutes, 30minutes, 20 minutes, or 10 minutes) after delivery. The target deployedviscosity can be high enough to cause an agglomeration of the embolicelement 230 to remain within the internal volume of the aneurysm withoutreinforcing the neck.

In at least some cases, the biopolymer has a non-zero degree of chemicalcrosslinking within the first precursor material 203 before mixing withthe chemical crosslinking agent. This can be useful, for example, tocustomize the curing window for the embolic element 230 so that itcorresponds well with an expected amount of time needed to deliver thematerial to the aneurysm. The degree of chemical crosslinking of thebiopolymer within the first precursor material 203 before mixing withthe chemical crosslinking agent, the ratio of the biopolymer to thechemical crosslinking agent, and/or one or more other variables can beselected to cause the embolic element 230 to have a viscosity suitablefor delivery to the aneurysm via the lumen of the conduit 116 for asuitable period of time (e.g., a period within a range from 10 minutesto 40 minutes) after mixing of the first and second precursor materials203, 205. In at least some cases, the first and second precursormaterials 203, 205 are mixed in proportions that cause a weight ratio ofthe biopolymer to the chemical crosslinking agent in the resultingembolic element 230 to be within a range from 10:1 to 100:1, such asfrom 10:1 to 30:1, or from 15:1 to 50:1, or from 15:1 to 25:1. In aparticular example, the first and second precursor materials 203, 205are mixed in proportions that cause a weight ratio of the biopolymer tothe chemical crosslinking agent in the resulting embolic element 230 tobe 30:1.

Use of a biopolymer instead of an artificial polymer in the firstprecursor material 203 may be advantageous because biopolymers tend tobe more readily bioabsorbed than artificial polymers and/or for otherreasons. Furthermore, use of a chemical crosslinking agent instead of aphysical crosslinking agent (i.e., a crosslinking agent that formsnoncovalent crosslinks between chains of the biopolymer) in the secondprecursor material 205 may be advantageous because chemicallycrosslinked polymers tend to be more cohesive than physicallycrosslinked polymers and/or for other reasons. In the context of forminga tissue scaffold within an aneurysm, high cohesiveness of the embolicelement 230 may be more important than it is in other contexts to securethe cured embolic element 230 within the aneurysm 302. For example, highcohesiveness of the embolic element 230 may reduce or eliminate thepossibility of a piece of the embolic element 230 breaking free andentering a patient's intracerebral blood stream during delivery.

The first and second precursor materials 203, 205 may include othercomponents and/or the system 200 may include other precursor materialsintended for mixing with the first and second precursor materials 203,205. For example, the first, second, and/or another precursor materialmay include a physical crosslinking agent. The presence of a physicalcrosslinking agent may be useful to form physical crosslinks thatcomplement chemical crosslinks from the chemical crosslinking agent. Thecombination of chemical and physical crosslinks may enhance thecohesiveness of the embolic element 230. Suitable physical crosslinkingagents for use with chitosan-based biopolymers include βglycerophosphate, mannitol, glucose, and derivatives and analogsthereof. In these and other cases, the embolic element 230 may includemultiple chemical crosslinking agents and/or multiple physicalcrosslinking agents.

A contrast agent is another component that may be added to the precursormaterials. The presence of a contrast agent within the embolic element230 can be useful to visualize delivery of the embolic element 230 usingfluoroscopy. One problem with using conventional platinum coils inintracranial aneurysms is that the persistent radiopacity of the coilstends to interfere with visualizing other aspects of the treatment infollow-up imaging. For example, the presence of platinum coils within ananeurysm may make it difficult or impossible to detect by fluoroscopythe presence of blood-carried contrast agent that would otherwiseindicate recanalization. In at least some embodiments of the presenttechnology, a contrast agent within the embolic element 230 is selectedto provide radiopacity that diminishes over time. For example, thecontrast agent may initially be radiopaque to facilitate delivery of theembolic element 230 and then become less radiopaque to facilitatefollow-up imaging. In a particular example, the first, second, and/oranother precursor material includes iohexol or a derivative or analogthereof as a suitable contrast agent.

In animal studies, the liquid embolics of the present technology wereshown to provide (a) complete or nearly complete volumetric filling ofthe aneurysm internal volume, and (b) complete or nearly completecoverage of the aneurysm neck with new endothelial tissue. Thesefeatures, among others, are expected to result in a lower recanalizationrate than that of platinum coil treatments and faster aneurysm occlusionthan that of flow diverters. Furthermore, the injectable scaffoldmaterial is expected to be bioabsorbed and thereby reduced in volumeover time. Thus, unlike platinum coils, the injectable scaffold isexpected to have little or no long-term mass effect. Furthermore, theinjectable scaffold material can be configured to have diminishingradiopacity; therefore, when so configured it will not interfere futureCT and MRI imaging and procedures. Embodiments of the present technologycan have these and/or other features and advantages relative toconventional counterparts whether or not such features and advantagesare described herein.

In some embodiments, the embolic kit 200 and/or embolic element 230 maybe any embolic or occlusive device, such as one or more embolic coils,polymer hydrogel(s), polymer fibers, mesh devices, or combinationsthereof. The embolic kit 200 may include one or more precursors that,once mixed together, form the embolic element 230 that remains withinthe aneurysm. In some embodiments, the embolic kit 200 may include theembolic element pre-mixed.

II. Selected Methods for Treating Aneurysms

FIGS. 3A-3G depict an example method for treating an aneurysm A with thesystems 10 of the present technology. To begin, a physician mayintravascularly advance the second elongated shaft 108 towards anintracranial aneurysm (or other treatment location such as any of thosedescribed herein) with the occlusive member 102 in a low-profile state.A distal portion of the second elongated shaft 108 may be advancedthrough a neck N of the aneurysm A to locate a distal opening of thesecond elongated shaft 108 within an interior cavity of the aneurysm A.The elongated member 106 may be advanced distally relative to the secondelongated shaft 108 to push the occlusive member 102 through the openingat the distal end of the second elongated shaft 108, thereby releasingthe occlusive member 102 from the shaft 108 and allowing the occlusivemember 102 to self-expand into a first expanded state.

FIG. 3A shows the occlusive member 102 in a first expanded state,positioned in an aneurysm cavity and still coupled to the elongatedmember 106. As shown in FIG. 3A, in the first expanded state, theocclusive member 102 may assume a predetermined shape that encloses aninternal volume 130 (see FIG. 1C). In this first expanded state, theocclusive member 102 may generally conform to the shape of the aneurysmA. As illustrated in FIG. 3B with the occlusive member 102 and deliverysystem shown in cross-section, the conduit 116 may be advanced throughthe internal volume 130 of the occlusive member 102 such that a distalopening of the conduit 116 is at or distal to the aperture 126 at thedistal portion of the occlusive member 102. The embolic element 230 maybe delivered through the conduit 116 to a space between the occlusivemember 102 and an inner surface of the aneurysm wall W.

In some embodiments, the method includes mixing the first and secondprecursor materials 203, 205 (FIG. 2 ) to form the embolic element 230.Mixing of the first and second precursor materials 203, 205 may occurprior to introducing the embolic element 230 to the treatment system 100and/or during delivery of the embolic element through the conduit 116 tothe aneurysm. In a particular example, the first precursor material 203is loaded into one of the barrels 214, the second precursor materials205 is loaded into the other barrel 214, and the mixing syringes 208 arecoupled via the coupler 210. To mix the first and second precursormaterials 203, 205, the plungers 212 are alternately depressed, therebycausing the first and second precursor materials 203, 205 to moverepeatedly from one barrel 214 to the other barrel 214. After suitablymixing the precursor materials, the resulting embolic element 230 can beloaded into the barrel 220 of the injection syringe 216. The injectionsyringe 216 may then be coupled to a proximal end of the conduit 116 todeliver the embolic element 230 through the conduit 116 and into theaneurysm A. As the embolic element 230 passes through the lumen of theconduit 116, chemical crosslinking of the biopolymer can continue tooccur.

Still with reference to FIG. 3B, as the embolic element 230 is deliveredbetween the dome of the aneurysm A and the distal portion 132 of thewall of the occlusive member 102, pressure builds between the aneurysmwall W and the occlusive member 102. As shown in the progression ofFIGS. 3B-3D, when the forces on the occlusive member 102 reach athreshold level, the embolic element 230 pushes the distal wall 132downwardly towards the neck N of the aneurysm A. The embolic element 230exerts a substantially uniform pressure across the distal surface of theocclusive member 102 that collapses the occlusive member 102 inwardly onitself such that the rounded distal wall 132 transitions from concavetowards the neck N of the aneurysm A to convex towards the neck N. Thepressure and inversion of the distal portion of the wall 132 creates anannular fold 136 that defines the distal-most edge of the occlusivemember 102. As the occlusive member 102 continues to invert, theposition of the fold 136 moves towards the neck N, which continues untila distal-most half of the occlusive member 102 has inverted. In someembodiments, the occlusive member 102 may include one or more portionsconfigured to preferentially flex or bend such that the occlusive member102 folds at a desired longitude. Moreover, as the occlusive member 102collapses, a distance between the wall at the distal portion 132 and thewall at the proximal portion decreases, and thus the internal volume 130of the occlusive member 102 also decreases. As the occlusive member 102collapses, the conduit 116 may be held stationary, advanced distally,and/or retracted proximally.

During and after delivery of the embolic element 230, none orsubstantially none of the embolic element 230 migrates through the poresof the occlusive member 102 and into the internal volume 130. Saidanother way, all or substantially all of the embolic element 230 remainsat the exterior surface or outside of the occlusive member 102.Compression of the occlusive member with the embolic element 230provides a real-time “leveling” or “aneurysm-filling indicator” to thephysician under single plane imaging methods (such as fluoroscopy) sothat the physician can confirm at what point the volume of the aneurysmis completely filled. Additional details regarding devices, systems, andmethods for monitoring and/or confirming deployment are described belowwith reference to FIGS. 4A-5B. It is beneficial to fill as much space inthe aneurysm as possible, as leaving voids within the aneurysm sac maycause delayed healing and increased risk of aneurysm recanalizationand/or rupture. While the scaffolding provided by the occlusive member102 across the neck helps thrombosis of blood in any gaps and healing atthe neck, the substantial filling of the cavity prevents rupture acutelyand does not rely on the neck scaffold (i.e., the occlusive member 102).Confirmation of complete or substantially complete aneurysm fillingunder single plane imaging cannot be provided by conventional devices.

Once delivery of the embolic element 230 is complete, the conduit 116may be withdrawn. In some embodiments, the embolic element 230 may fillgreater than 40% of the aneurysm sac volume. In some embodiments, theembolic element 230 may fill greater than 50% of the aneurysm sacvolume. In some embodiments, the embolic element 230 may fill greaterthan 60% of the aneurysm sac volume. In some embodiments, the embolicelement may fill greater than 65%, 70%, 75%, 80%, 85%, or 90% of theaneurysm sac volume.

FIG. 3E shows a second expanded state of the occlusive member 102, shownin cross-section, with the embolic element 230 occupying the remainingvolume of the aneurysm A. FIG. 3F shows the occlusive member 102 in fullwith the embolic element 230 removed so the second shape of theocclusive member 102 is visible. As shown, the embolic element 230 maybe delivered until the occlusive member 102 is fully-collapsed such thatthe occlusive member 102 has substantially no internal volume.

In the second expanded state, the occlusive member 102 may form a bowlshape that extends across the neck of the aneurysm A. The wall of theocclusive member 102 at the distal portion may now be positioned incontact with or immediately adjacent the wall of the occlusive member102 at the proximal portion. The distal wall 132 may be in contact withthe proximal wall 134 along all or substantially all of its length. Insome embodiments, the distal wall 132 may be in contact with theproximal wall 134 along only a portion of its length, while theremainder of the length of the distal wall 132 is in close proximity—butnot in contact with—the proximal wall 134.

Collapse of the occlusive member 102 onto itself, towards the neck N ofthe aneurysm, may be especially beneficial as it doubles the number oflayers across the neck and thus increases occlusion at the neck N. Forexample, the distal wall 132 collapsing or inverting onto the proximalwall 134 may decrease the porosity of the occlusive member 102 at theneck N. In those embodiments where the occlusive member 102 is a mesh orbraided device such that the distal wall 132 has a first porosity andthe proximal wall 134 has a second porosity, deformation of the distalwall 132 onto or into close proximity within the proximal wall 134decreases the effective porosity of the occlusive member 102 over theneck N. The resulting multi-layer structure thus has a lower porositythan the individual first and second porosities. Moreover, the embolicelement 230 along the distal wall 132 provides additional occlusion. Insome embodiments, the embolic element 230 completely or substantiallycompletely occludes the pores of the adjacent layer or wall of theocclusion member 102 such that blood cannot flow past the embolicelement 230 into the aneurysm cavity. It is desirable to occlude as muchof the aneurysm as possible, as leaving voids of gaps can allow blood toflow in and/or pool, which may continue to stretch out the walls ofaneurysm A. Dilation of the aneurysm A can lead to recanalization and/orherniation of the occlusive member 102 and/or embolic element 230 intothe parent vessel and/or may cause the aneurysm A to rupture. Bothconditions can be fatal to the patient.

In those embodiments where the wall of the occlusive member 102comprises an inner and outer layer, the deformed or second shape of theocclusive member 102 forms four layers over the neck N of the aneurysm AIn those embodiments where the wall of the occlusive member 102comprises a single layer, the deformed or second shape of the occlusivemember 102 forms two layers over the neck N of the aneurysm A Aspreviously mentioned, the neck coverage provided by the doubled layersprovides additional surface area for endothelial cell growth, decreasesthe porosity of the occlusive member 102 at the neck N (as compared totwo layers or one layer), and prevents herniation of the embolic element230 into the parent vessel. During and after delivery, the embolicelement 230 exerts a substantially uniform pressure on the occlusivemember 102 towards the neck N of the aneurysm A, thereby pressing theportions of the occlusive member 102 positioned adjacent the neckagainst the inner surface of the aneurysm wall such that the occlusivemember 102 forms a complete and stable seal at the neck N.

As shown in FIG. 3G, the first coupler 112 may be detached from thesecond coupler 114 and the elongated member 106 and second elongatedshaft 108 may be withdrawn, thereby leaving the occlusive member 102 andembolic element 230 implanted within the aneurysm A.

Over time natural vascular remodeling mechanisms and/or bioabsorption ofthe embolic element 230 may lead to formation of a thrombus and/orconversion of entrapped thrombus to fibrous tissue within the internalvolume of the aneurysm A. These mechanisms also may lead to cell deathat a wall of the aneurysm and growth of new endothelial cells betweenand over the filaments or struts of the occlusive device 102.Eventually, the thrombus and the cells at the wall of the aneurysm mayfully degrade, leaving behind a successfully remodeled region of theblood vessel.

In some embodiments, contrast agent can be delivered during advancementof the occlusive member 102 and/or embolic element 230 in thevasculature, deployment of the occlusive member 102 and/or embolicelement 230 at the aneurysm A, and/or after deployment of the occlusivemember 102 and/or embolic element 230 prior to initiation of withdrawalof the delivery system. The contrast agent can be delivered through thesecond elongated shaft 108, the conduit 116, or through another catheteror device commonly used to delivery contrast agent. The aneurysm (anddevices therein) may be imaged before, during, and/or after injection ofthe contrast agent, and the images may be compared to confirm a degreeof occlusion of the aneurysm.

According to some aspects of the technology, the system 10 may compriseseparate first and second elongated shafts (e.g., microcatheters) (notshown), the first dedicated to delivery of the embolic element, and thesecond dedicated to the delivery of the occlusive member. In examplemethods of treating an aneurysm, the first elongated shaft may beintravascularly advanced to the aneurysm and through the neck such thatthat a distal tip of the first elongated shaft is positioned within theaneurysm cavity. In some embodiments, the first elongated shaft may bepositioned within the aneurysm cavity such that the distal tip of theshaft is near the dome of the aneurysm.

The second elongated shaft containing the occlusive member (such asocclusive member 102) may be intravascularly advanced to the aneurysmand positioned within the aneurysm cavity adjacent the first elongatedshaft. The occlusive member may then be deployed within the aneurysmsac. As the occlusive member is deployed, it pushes the first elongatedshaft outwardly towards the side of the aneurysm, and when fullydeployed the occlusive member holds or “jails” the first elongated shaftbetween an outer surface of the occlusive member and the inner surfaceof the aneurysm wall.

The embolic element (such as embolic element 230) may then be deliveredthrough the first elongated shaft to a position between the innersurface of the aneurysm wall and the outer surface of the occlusivemember. For this reason, it may be beneficial to initially position thedistal tip of the first elongated shaft near the dome (or more distalsurface) of the aneurysm wall. This way, the “jailed” first elongatedshaft will be secured by the occlusive member such that the embolicelement gradually fills the open space in the aneurysm sac between thedome and the occlusive member. As described elsewhere herein, thefilling of the embolic element pushes and compresses the occlusivemember against the tissue surrounding the aneurysm neck as the space inthe sac above the occlusive member is being filled from the dome to theneck. Also as described elsewhere herein, the compression of theocclusive member with the embolic element provides a “leveling oraneurysm filling indicator” which is not provided by conventional singleplane imaging methods. The filling of the embolic element may complete,for example, when it occupies about 50-80% of the volume of theaneurysm.

III. Selected Devices, Systems, and Methods for Monitoring Deployment

Proper deployment of the embolic element 230 and the occlusive member102 can be monitored and/or confirmed using one or more medical imagingtechniques, such as fluoroscopy. FIGS. 4A-5B illustrate examples ofvarious types of fluoroscopic images that may be employed by a physicianat different stages of deployment to monitor the position of theocclusive member 102 within the aneurysm A, monitor the degree offilling of the aneurysm A with the embolic element 230, and/or confirm adegree of occlusion of the aneurysm A by the deployed system. Asdescribed in greater detail below, the devices and systems of thepresent technology may be configured to provide unique visual indicatorsthat provide confirmation to the physician via one or more medicalimaging techniques regarding a degree of occlusion of the aneurysm. Asdescribed in greater detail below, the visual indicators may include aparticular change in shape of all or a portion of the occlusive member102, a particular change in relative position of one or more radiopaquemarkers on the occlusive member 102 and/or delivery system (such as theconduit 116), a particular change in shape of the embolic element 230,and others.

Although the following discussion is made with reference to thetwo-dimensional images shown in FIGS. 4A-5B, the systems and methods ofthe present technology can be employed with three-dimensional imagingtechniques. Moreover, FIGS. 4A-5B represent a two-dimensional image inwhich only a slice of the aneurysm (and devices therein) is visible.While in some cases the inner and outer layers of the occlusive member102 (when such are present) may be distinguishable from one another inthe radiographic image, in the present example the layers appear as onethick layer. As used herein, “proper deployment” or “successfuldeployment” may refer to (a) complete (e.g., greater than 80%) orsubstantially complete (e.g., greater than 50%) filling of the aneurysmA with the embolic element 230, (b) complete or substantially completeinversion or collapse of the occlusive member 102 onto itself over theneck N of the aneurysm A, (c) or both.

The occlusive member 102 may include one or more radiopaque markers,such as markers 402, 404, 406, and 114 (referred to collectively as“markers 401”) shown in FIGS. 4A-4C. The markers 401 may be disposedabout the occlusive member 102 in a specific spatial arrangement suchthat relative movement of the markers is indicative of a degree of stageof deployment of the occlusive member 102 and/or embolic element 230.The markers 401 may be positioned at any location along the occlusivemember 102. For example, the occlusive member 102 may include one ormore radiopaque markers 402 at or along its distal wall 132 (only oneshown for ease of illustration), one or more radiopaque markers 404 ator along its proximal wall 134 (only one shown for ease ofillustration), and one or more radiopaque markers 406 at or along theintermediate portion of the wall (only one shown for ease ofillustration). Moreover, the coupler 114 of the occlusive member 102 maybe radiopaque. The markers 401 may be positioned at one, some, or all ofthe layers of the occlusive member 102 (at least in those embodimentswhere the occlusive member 102 includes multiple layers). In someembodiments, the individual markers 401 may comprise a radiopaque bandor clip coupled to the one or more struts, filaments, wires, etc. of theocclusive member 102. In some embodiments, the individual markers 401may comprise a radiopaque material coated on or otherwise incorporatedinto the wall of the occlusive member 102. The individual markers 401may have the same or different shapes, lengths, and/or profiles.

In some embodiments, in addition to or instead of having one or moremarkers 401, the occlusive member 102 itself may be partially orcompletely formed of a radiopaque material, such as one or moreradiopaque wires. In the example depicted in FIGS. 4A-4C, the occlusivemember 102 is formed of a radiopaque material and also includesradiopaque markers 402, 404, 406. The occlusive member 102 is formed ofa plurality of drawn-filled tube (“DFT”) wires, which comprise a coreformed of a radiopaque material (such as platinum) surrounded by anouter non-radiopaque material (at least relative to the core material).The markers 402, 404, 406 are completely formed of a radiopaque materialand thus have a higher density of radiopaque material. As such, themarkers 402, 404, 406 appear darker than the occlusive member 102 in theimages. In some embodiments, the occlusive member 102 may have aradiopacity that is different than the radiopacity of one or more of themarkers 402, 404, 406 such that the wall of the occlusive member 102wall and the marker(s) 406 can be distinguished from one another on theradiographic image. The wall of the occlusive member 102 may be more orless radiopaque than one or more of the markers 402, 404, 406.

In some embodiments, one or more components of the delivery system mayinclude one or more radiopaque markers. For example, the conduit 116 mayinclude one or more radiopaque markers positioned along its length. Inthe embodiment depicted in FIGS. 4A-4C, the conduit 116 may include aradiopaque marker 400 positioned at or near its distal end. The conduit116 may have one or more additional markers (not shown) positioned alongits length, such as along the length of the conduit 116 that extendsthrough the interior volume 130 of the occlusive member 102.

As shown in FIG. 4A, when the occlusive member 102 is first deployed(e.g., allowed to self-expand) within the aneurysm, the radiopaquemarker(s) 402, 404, 406 of the occlusive member 102 will be in a firstposition relative to one another, and to the radiopaque marker(s) of theconduit 116. By way of example, markers 402 and 404 are separated by afirst distance d₁ when the occlusive member 102 is first deployed. Asthe embolic element 230 is conveyed through the conduit 116 and into theaneurysm sac, the occlusive member 102 may deform as describedpreviously with respect to FIGS. 3A-3G. This deformation can cause theradiopaque marker(s) 401 carried by the occlusive member 102 to move toa second position relative to one another. For example, the physicianmay confirm progression of deployment by observing that markers 402 and404 are now separated by a distance d₂. The radiopaque marker(s) 401 mayalso move relative to the radiopaque marker(s) 400 of the conduit 116,which may remain in the same or substantially the same place within theaneurysm. By comparing an image of the radiopaque markers 400 and/or 401in the first relative positions and an image of the radiopaque markers400 and/or 401 in the second relative positions, a clinician canvisually confirm that the embolic element 230 has filled a certainpercentage of the aneurysm A.

For example, according to some aspects of the technology, confirmationof sufficient filling of the aneurysm (i.e., 50% or greater) may beindicated by one or more distal wall markers 402 moving into closeproximity to one or more proximal wall markers 404 and/or touching oneor more proximal wall markers 404. Because the embolic element 230applies a generally uniform pressure across the distal wall 132 andpushes downwardly towards the neck N as it fills in the space betweenthe occlusive member 102 and the aneurysm wall, the movement of one ormore distal wall markers 402 to a position adjacent a proximal wallmarker 404 indicates to a physician that the aneurysm A is substantiallyfilled (e.g., 50% or greater) with the embolic element 230. Thisrelative positioning also indicates that the distal wall 132 is nowproviding additional occlusion at the neck N of the aneurysm and thatthe occlusive member 102 is in its second expanded shape. In someembodiments, the coupler 114 may be used as the proximal indicatorinstead of or in addition to the one or more proximal markers 404.

In some embodiments, confirmation of sufficient filling of the aneurysm(i.e., 50% or greater) may be indicated by one or more distal wallmarkers 402 moving away from the conduit marker 400 (or marker affixedto another component of the delivery system) by a predetermineddistance. For example, when the occlusive member 102 is in the firstexpanded state or shape (FIG. 4A) the distal wall marker 402 may beadjacent the conduit marker 400. In the second expanded state or shape(FIG. 4C), the distal wall marker 402 may be separated from the conduitmarker 400 by a distance that is generally equivalent to a diameter D ofthe occlusive member 102 in its expanded state while initiallypositioned in the aneurysm A. As explained above, such relativepositioning of one or more distal wall markers 402 and conduit marker400 indicates to a physician that the aneurysm A is substantially filled(e.g., 50% or greater) with the embolic element 230. This relativepositioning also indicates that the distal wall 132 is now providingadditional occlusion at the neck N of the aneurysm and that theocclusive member 102 is in its second expanded shape.

In some embodiments, one or more intermediate markers 406 may be used toconfirm and/or monitor deployment. For example, one or more intermediatemarkers 406 may be positioned at or near a desired inversion plane ofthe occlusive member 102. In the present example using a generallyspherical occlusive member 102 that deforms to assume a bowl shape, theinversion plane is at or near a midline of the occlusive member 102 inits expanded state. This is because, in a fully inverted state, thedistal half of the occlusive member 102 will lie within/conform to theproximal half of the occlusive member 102 (as shown in FIG. 4C). Assuch, the midline of the occlusive member 102 is the desired plane ofinversion. The occlusive member 102 may be radiopaque (as shown in FIGS.4A-4C), but to a lesser extent than the intermediate marker(s) 406 suchthat the occlusive member 102 wall and the marker(s) 406 can bedistinguished from one another on the radiographic image. As such, animage showing the top edge 136 (FIG. 4C) of the occlusive member 102adjacent or at the intermediate marker(s) 406 may indicate that theaneurysm A is substantially filled (e.g., 50% or greater) with theembolic element 230. This relative positioning also indicates that thedistal wall 132 is now providing additional occlusion at the neck N ofthe aneurysm and that the occlusive member 102 is in its second expandedshape.

The change in shape of the occlusive member 102 and/or change inposition of different portions of the occlusive member 102 relatively toone another may also indicate proper deployment. As previouslydiscussed, the occlusive member 102 assumes a first expanded shape wheninitially deployed and has a second expanded shape after deformation bythe embolic element 230. In several embodiments, the second expandedshape represents a partially or completely inverted from of the firstexpanded shape, which can be confirmed on the radiographic image byobserving the changing outline of the occlusive member 102. Forinstance, in the present example where the occlusive member 102 has afirst expanded shape that is generally spherical, an image showing aC-shape (as shown in FIG. 4C) may indicate that the desired fillingand/or deployment is complete. In a three-dimensional image, the secondexpanded shape may have a bowl shape. In some embodiments, confirmationof complete or substantially complete deployment may be indicated by thedistal wall 500 being within a predetermined distance of the proximalwall 502.

In some embodiments, proper deployment may be confirmed by observing adistance between the inverted wall (here, distal wall 132) and therelatively stationary wall (here, proximal wall 134). As shown in FIG.4C, when the distal wall 132 collapses down onto or near the proximalwall 134, the occlusive member 102 presents on the image as having twicethe thickness at the proximal portion. Moreover, as the occlusive member102 inverts, the density of the radiopaque material doubles, and thusthe doubled-over portions of the occlusive member 102 appear darker onthe image.

As shown in FIGS. 5A and 5B, in some embodiments, certain portions ofthe occlusive member 102 may be coated with a radiopaque material suchthat change in shape or orientation of those portions indicates adesired position of the occlusive member 102. For example, as shown inFIG. 5A, a distal-most half 500 of the occlusive member 102 may becoated with a radiopaque material while a proximal-most half 502 may notbe coated or may otherwise be less radiopaque than the distal half 500.As such, confirmation of complete or substantially complete deploymentmay be indicated by the more radiopaque distal wall 500 being adjacentthe proximal wall 502. For example, confirmation of complete orsubstantially complete deployment may be indicated by the distal wall500 being within a predetermined distance of the proximal wall 502.Confirmation may also be gleaned from the distal wall 500 changing inshape from flat or convex (towards the dome) of the aneurysm A toconcave.

A shape of the embolic element 230 may also provide an indication ofdeployment progress. For example, the shape of the lower (closer to theneck N) perimeter of the aneurysm A can be indicative of a degree offilling of the aneurysm with the embolic element 230 and/or degree ofdeformation of the occlusive member 102. As most aneurysms have agenerally spherical or globular shape, a lower boundary of the embolicelement 230 may have a decreasing radius of curvature as more isinjected and more of the occlusive member 102 inverts. For example, inFIG. 4B, when the aneurysm A is partially filled with the embolicelement 230 and the occlusive member 102 is only partially collapsed orinverted, the distal wall 132 has a first radius of curvature. In FIG.4C, when the aneurysm A is substantially completely or completelyfilled, the distal wall 132 has a radius of curvature less than theradius of curvature of the distal wall 132 in the partially deformedstate.

Additionally or alternatively, the degree of deployment of the occlusivemember 102 and/or degree of filling of the aneurysm A can be furtherdetermined by injecting contrast into the parent blood vessel andimaging the aneurysm to determine how much of the contrast enters theaneurysm cavity. The shape of the

The devices, systems, and methods of the present technology may beparticularly beneficial over conventional devices for two-dimensionalimaging. In two-dimensional imaging (such as fluoroscopy), the image mayreflect only a slice or elevational view of the aneurysm (and device orsubstance therein). As such, any voids or gaps in filling may not beapparent in the slice because the image slice does not transect the voidwithin the aneurysm A, or the cross-section or elevational view of thestagnated area may take on different shapes depending on how the imageis observed. A physician may have to take a plurality of images todetermine a general amount of filling in the aneurysm. In contrast, theocclusion members 102 of the present technology have a unique shape thatdynamically adjusts to the introduction of an embolic element 230 in apredictable, measurable way that indicates a degree of filling of theembolic element 230 in a single two-dimensional radiographic image.

The devices, systems, and methods disclosed herein include confirmingand/or observing various stages of deployment of the system in ananeurysm, including complete or substantially complete deployment, usingone, some, or all of the methods disclosed above.

CONCLUSION

The descriptions of embodiments of the technology are not intended to beexhaustive or to limit the technology to the precise form disclosedabove. Where the context permits, singular or plural terms may alsoinclude the plural or singular term, respectively. Although specificembodiments of, and examples for, the technology are described above forillustrative purposes, various equivalent modifications are possiblewithin the scope of the technology, as those skilled in the relevant artwill recognize. For example, while steps are presented in a given order,alternative embodiments may perform steps in a different order. Thevarious embodiments described herein may also be combined to providefurther embodiments.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the term “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

We claim:
 1. A method for treating an aneurysm, the method comprising:positioning a distal end of an elongated shaft in an aneurysm cavity;releasing an occlusive member from the elongated shaft while the distalend of the elongated shaft is positioned within the aneurysm cavity suchthat the occlusive member self-expands to assume a first expanded statein which the occlusive member forms a first shape, wherein, in the firstexpanded state, the occlusive member encloses an interior region havinga first interior volume; and delivering an embolic element between theocclusive member and the aneurysm wall to transform the occlusive memberinto a second expanded state in which the occlusive member encloses asecond interior volume less than the first interior volume, wherein theocclusive member forms a second shape in the second expanded state thatis different than the first shape in the first expanded state; andwherein transforming the occlusive member into the second expanded shapeincludes injecting the embolic element to invert a portion of a sidewallof the occlusive member such that the portion is convex towards theaneurysm wall in the first expanded state and concave towards theaneurysm wall in the second expanded state.
 2. The method of claim 1,wherein transforming the occlusive member into the second expanded shapeincludes injecting the embolic element to urge a portion of a sidewallof the occlusive member in a direction away from the aneurysm wall andtowards the interior region of the occlusive member.
 3. The method ofclaim 1, wherein transforming the occlusive member into the secondexpanded shape includes injecting the embolic element to invert aportion of a sidewall of the occlusive member such that the portion isconvex towards the aneurysm wall in the first expanded state and concavetowards the aneurysm wall in the second expanded state.
 4. The method ofclaim 1, wherein the embolic element comprises a liquid embolic.
 5. Themethod of claim 1, wherein delivering the embolic element occurs afterthe occlusive member is in the first expanded state.
 6. The method ofclaim 1, wherein the occlusive member has a globular or generallyspherical shape in the first expanded state and a cup or bowl-shape inthe second expanded state.
 7. The method of claim 1, wherein the embolicelement comprises a biopolymer and a chemical crosslinking agent.
 8. Themethod of claim 7, wherein the biopolymer includes chitosan, aderivative of chitosan, an analog of chitosan, or a combination thereof;and the chemical crosslinking agent includes genipin, a derivative ofgenipin, an analog of genipin, or a combination thereof; wherein theembolic element further comprises a physical crosslinking agent includesβ glycerophosphate, a derivative of β glycerophosphate, an analog of βglycerophosphate, or a combination thereof.
 9. The method of claim 8,wherein the embolic element comprises a contrast agent.
 10. The methodof claim 1, wherein the occlusive member is a braid.
 11. The method ofclaim 1, wherein the embolic element comprises a coil.
 12. A method fortreating an aneurysm, the method comprising: positioning an expandableocclusive member in an initial expanded state within an aneurysm,wherein in the initial expanded state the occlusive member provides anumber of layers across a neck of the aneurysm; and doubling the numberof layers of the occlusive member across the neck of the aneurysm byintroducing an embolic element to an aneurysm cavity.
 13. The method ofclaim 12, wherein the number of layers after doubling is two.
 14. Themethod of claim 12, wherein the number of layers after doubling is four.15. The method of claim 12, wherein the occlusive member has a firstshape in the initial expanded state, and wherein introducing the embolicelement transforms the occlusive member from the initial expanded stateto a secondary expanded state in which the occlusive member forms asecond shape different than the first shape.
 16. The method of claim 15,wherein a volume enclosed by the first shape is greater than a volumeenclosed by the second shape.
 17. The method of claim 15, whereintransforming the occlusive member into the second expanded shapeincludes injecting the embolic element to urge a portion of a sidewallof the occlusive member in a direction away from the aneurysm wall andtowards an interior region of the occlusive member.
 18. The method ofclaim 12, wherein the occlusive member is a braid.
 19. The method ofclaim 12, wherein the embolic element comprises a coil.